tbuckley/cabot-search huggingface dataset:
Abstract 13379: Perceived Stress and Cardiovascular Risk Among Older Persons With HIV
Authors: Megan E Mayfield, Drenna Waldrop, Sudeshna Paul, Rebecca A Gary
Journal: Circulation (2022)

Background: Cardiovascular disease (CVD) is highly prevalent among older persons with HIV (OPWH) occurring on average a decade earlier than non-infected individuals largely due to chronic inflammation, vascular pathology, and psychosocial stressors. Effective cardiovascular risk reduction strategies such as exercise have been shown to lower both physiological and psychosocial stressors but have not been widely reported in the HIV population. Objective: To evaluate the effect of a one-year, moderate intensity aerobic exercise intervention on perceived stress among OPWH with ≥ 2 CVD risk factors. Methods: A secondary analysis was performed utilizing data from Project FiTBRAiN, a 2-arm RCT that included Let’s Move (moderate intensity aerobic exercise intervention) or Let’s Flex (flexibility/stretching attention control) groups. The 14-item Perceived Stress Scale (PSS) was utilized to measure participants’ perceived stress. Data analysis included an analysis of variance with pairwise and between-group differences reported. Results: Participants (n=115) reported a mean age of 55±5.2, and the majority were African American (n=100, 87.0%) and male (n=66, 57.4%). The most common cardiovascular comorbidities were elevated: total cholesterol (n=114, 99.1%), systolic blood pressure (n=108, 93.9%), diastolic blood pressure (n=98, 85.2%), and participants had a mean BMI of 28.29. Baseline 14-item PSS scores for the Let’s Move Program and Let’s Flex Program were 19.49 (SD=7.94) and 21.13 (SD=8.64), respectively, indicating moderate stress levels. Over all time points, the control group (Let’s Flex) had higher perceived stress than the intervention group (Let’s Move), but were not significant. Conclusions: Our findings suggest that moderate levels of psychological stress were present in this population and may be a risk factor for CVD among OPWH. The consistent finding that perceived stress remained lower over time indicates that aerobic exercise may be beneficial for stress reduction. Additional research is needed to determine the optimal dose and mode of exercise that is most beneficial for stress reduction in this population.
Abstract 14644: The Association Between Neighborhood Distress and Outcomes Following Peripheral Vascular Intervention
Authors: Eric Strand, Kim G Smolderen, Gaelle Romain, Matthew Burg, Kamil Faridi, Keith B Churchwell, Carlos Mena-Hurtado
Journal: Circulation (2022)

Introduction: Peripheral arterial disease (PAD) is associated with an elevated risk of mortality. Low socioeconomic status (SES) is associated with increased prevalence and severity of PAD, and low SES has been associated with poor post procedural outcomes in cardiovascular disease. The Distressed Communities Index (DCI) uses seven common proxies of SES, such as educational attainment, housing stability, median income, and employment rate, to generate an aggregate score at a zip code level. Hypothesis: We hypothesized that increased levels of neighborhood distress, as measured by the DCI, is associated with an increased risk of mortality and amputation after PVI. Methods : We queried the Vascular Quality Initiatives (VQI) database, linked with Medicare claims data for patients who had undergone PVI. A total of 16,980 patients with PVI were found and 53 Excluded because ≥ 1 missing data for covariate used in modelling and 381 because DCI Missing. Patient 5-digit zip codes were used to obtain a DCI score (range 1-100, with higher scores indicating greater distress) from the Economic Innovation group. We examined the association between DCI and 2-year mortality and major amputation. Results: At 24 months, 2 964 (17.5%) had died 1 669 (9.9%) and had a major amputation DCI score was positively associated 2-year mortality risk. A 10-point higher DCI score was associated with increased mortality risk (unadjusted HR=1.02; 95%CI [1.01,1.03]) and a higher risk of amputation (unadjusted HR=1.05; 95%CI [1.04,1.07]). Fig. Conclusions: Higher level of community deprivation was associated with increased risk of short-and long-term mortality and amputation outcomes following PVI. PAD care pathways should integrate improved risk assessments and integrated care models for patients from distressed communities to help address health disparities.
Abstract 14913: Renal Function Underpins Cox-2: Methylarginine Axis in Mouse and Man
Authors: Plinio M Ferreira, Nicholas Kirkby, Ricky Vaja, Maria Lopes Pires, Marilena Crescente, Bin Liu, He Yu, Melissa Chan, Rolf Nuesing, Yongbi Zhou, William White, Elizabeth Want, Tim D Warner, rebecca knowles, magdi yaqoob, Hillary Longhurst, Anran Zhang, Matthew Rickman
Journal: Circulation (2022)

Introduction and Hypothesis: Through the production of prostacyclin (PGI2), cyclooxygenase (COX)-2 protects the cardio-renal system. Restraining methylarginines (ADMA, SDMA), which are biomarkers of renal and cardiovascular disease and inhibitors (ADMA) of cardioprotective endothelial nitric oxide synthase (eNOS), has been suggested as a contributory pathway. However, the relationship between renal function, COX-2 and methylarginines remains unclear. Methods: Using plasma from genetically modified mice with germline global deletion of COX-2 or PGI 2 synthase (PGIS) and human plasma from a unique individual lacking COX-derived prostaglandins due to a loss of cPLA 2 , before and after receiving a cPLA 2 -replete transplanted donor kidney, we measured methylarginines, arginine and citrulline using UHPLC-MS/MS. Renal function was assessed by measuring cystatin C by ELISA. To eliminate the impact of renal function in vivo , methylarginine and PGI 2 release from organotypic kidney slices in culture were quantified by ELISA. Results: Plasma ADMA, SDMA, citrulline and cystatin C, were similarly elevated in samples from the patient lacking COX/PGI 2 capacity compared to levels in healthy volunteers. Renal function, ADMA, SDMA and citrulline returned towards normal range when the patient received a genetically normal kidney, capable of COX/PGI 2 activity. Cystatin C correlated with ADMA, SDMA and citrulline. Loss of COX-2 or PGIS in mice increased plasma levels of ADMA, SDMA and cystatin C. As in human, SDMA, ADMA and citrulline but not arginine positively correlated with cystatin C. Levels of analytes in conditioned media of kidney slices (24h) were not altered in tissue from COX-2 KO (6-keto=14.0±1.8, ADMA=1.0±0.06, SDMA=0.30±0.05; n=8) compared to wildtype mice (66-keto=15.0±1.7, ADMA=0.98±0.06, SDMA=0.24±0.01; n=12). Conclusions: COX-2 and PGI2 are critical regulators of renal function. Plasma methylarginines are integrally linked to renal homeostasis.
Abstract 14453: Deep Learning Enabled Measurement of Cardiac Sphericity Predicts Disease Risk Among Subjects With Normal Left Ventricular Size and Function
Authors: Milso Vukadinovic, Alan C Kwan, Michael Salerno, Daniel C Lee, Christine M Albert, Susan Cheng, Debiao Li, David Ouyang, Shoa L Clarke
Journal: Circulation (2022)

Introduction: Cardiac imaging primarily focuses on measurements of chamber size and function. Quantitative assessment of morphology may provide additional prognostic information. Left ventricle (LV) sphericity has been proposed as one metric but has not been studied in large populations and is poorly characterized in patients with normal LVs. We aimed to assess the clinical relevance and genetic drivers of sphericity among individuals with normal LV size and systolic function using deep learning enabled phenotyping of cardiac MRIs. Methods: The study cohort consisted of UK Biobank participants with normal LV ejection fraction, LV end-systolic, and end-diastolic volumes by MRI. A fully convolutional neural network was used to perform image segmentation of cardiac chambers. The main exposure was the LV sphericity index, defined as the ratio of short-axis to long-axis lengths of the smallest rectangle encompassing the LV in a 4-chamber view. Risk for incident outcomes were measured using Cox analysis. Genome-wide association study (GWAS) was performed using HAIL software with standard quality-control. Genetic correlations were measured using linkage-disequilibrium score regression. Causal inference was performed using two-sample Mendelian randomization (MR). Results: We identified 38,897 subjects with normal LV volumes and ejection fraction. Mean age was 55 ± 8, and 54% were female. After adjusting for age, sex, BMI, hypertension, and pulse-rate, a 1 standard deviation increase in sphericity index was associated with increased risk of atrial fibrillation (HR 1.31, 95% CI 1.23-1.38, P &lt;2x10 -16 ) and cardiomyopathy (HR 1.62, 95% CI 1.29-2.02, P 2.4x10 -5 ). GWAS of sphericity index identified 4 loci at genome-wide significance, with 3 candidate genes previously implicated in cardiac development and conduction. Sphericity index showed a genetic correlation with cardiomyopathy ( rg 0.42, P 0.01) but not with atrial fibrillation ( rg 0.04, P 0.5). Bidirectional MR analyses supported cardiomyopathy as being causal for sphericity but not the reverse. Conclusion LV sphericity in subjects with normal size and function is genetically mediated and may reflect subclinical manifestations of cardiomyopathic risk prior to LV remodeling by standard measures.
Abstract 15313: Hypoglycemia: The Forgotten "H&amp;T" in Cardiac Arrest
Authors: Hui Chong Lau, Sze Jia Ng, Subha Saeed, Muhammad Moiz Tahir, Swe Swe Hlaing, Navjot Rai, Rahul Gaiba
Journal: Circulation (2022)

Introduction: Hypoglycemia is known to cause cardiac arrhythmias and even sudden cardiac death by inducing oxidative stress, QT prolongation, and myocardial injury. Chromosomal deletion of 1p36 is associated with learning difficulty, progressive renal disease, and cardiomyopathy. To our knowledge, this is the first case of a patient with 1p36 deletion syndrome and end-stage renal disease (ESRD) who developed cardiac arrest due to hypoglycemia. Case Presentation: A 26-year-old female presented to the emergency department with generalized itching, weakness, and progressive dyspnea after missing multiple hemodialysis (HD) sessions. She was admitted for HD and her stay was complicated by an episode of coffee-ground emesis and she was nil per oral (NPO) for an endoscopy. That night, the patient became bradycardic and had a cardiac arrest with pulseless electrical activity (PEA). Fingerstick blood glucose was undetectable during resuscitation and ROSC was achieved instantaneously after dextrose administration. The patient had no history of diabetes and was refusing glucose checks while NPO. She had a remarkable neurological recovery post-cardiac arrest. However, her glucose levels remained persistently low despite maximally tolerated feeds. An extensive workup for persistent hypoglycemia including peptide C levels, hba1c, and insulin level were within normal limits. Her cortisol level was appropriately raised. CT scan of the head performed was normal. Cardiac catheterization revealed no coronary artery disease. Discussions: Hypoglycemia was removed from the Advanced Cardiovascular Life Support (ACLS) algorithm as a reversible cause of cardiac arrest in 2010. Our case is a reminder of a life-threatening yet quickly reversible cause of cardiac arrest. Conclusions: ESRD increases the risk of hypoglycemia due to decreased insulin clearance and must be carefully monitored while NPO. Physicians have to be aware that routine dextrose administration during cardiac resuscitation does not improve survival and neurological outcomes.
Abstract 15584: Metabolomic Signature of Fontan Circulation
Authors: Ashish H Shah, Amir Ravandi, Michel Aliani
Journal: Circulation (2022)

Introduction: Patients born with a range of cardiac defects, not amenable to biventricular repair are palliated with establishment of Fontan circulation. Although majority of patients with Fontan circulation survive childhood, eventually they experience multi-system dysfunction, mainly frailty, impaired exercise capacity, blunted exercise-augmented hemodynamics, progressive liver fibrosis, and shortened survival. Fontan circulation associated biochemical abnormalities have not been well described. Materials and Methods: Twenty adult patients with Fontan circulation and 20 age- and sex-matched healthy subjects underwent a non-targeted metabolomics assessment using an LC-QTOF-MS system to detect potential Fontan-related biomarkers. These study participants were also investigated for markers of frailty, cardiopulmonary exercise testing, and resting as well as exercise-augmented hemodynamic evaluation. Results: A total of 1679 known plasma metabolites were detected in electrospray positive and negative modes among which 37 metabolites were significantly different (T-Test Unpaired (p&lt;0.05) followed by a multiple testing correction of p values (Benjamini-Hochberg)). These metabolites belonged to several classes of compounds including lipids, bile acids, amino acids, and derivatives. Several bile acids such as chenodeoxycholic acid glycine conjugate, glycoursodeoxycholic acid, and deoxycholic acid glycine conjugate were upregulated in patients with Fontan while 8-hydroxyguanine, N-arachidonoyl glycine, uracil, and cysteine were down-regulated in comparison to healthy subjects. Conclusion: In-depth plasma metabolomic analysis demonstrated metabolic pathways activation involved in bile acid formation, markers of oxidative stress, damage of DNA, whereas lower concentrations of several amino acids in patients with Fontan.
Abstract 14550: A Decade Trend, Sex, Racial and Socioeconomic Disparities Amongst Patients Hospitalized for Premature Myocardial Infarction in the United States
Authors: IRIAGBONSE ASEMOTA, Emmanuel Akuna, Bharosa Sharma, Hasan Hammo, Muhammad Khawar Sana, Muhammad Usman Almani, San Deangelo, Mahir Yilmaz
Journal: Circulation (2022)

Introduction: Acute myocardial infarction (AMI) is the leading cause of premature morbidity and premature death worldwide. Premature myocardial Infarction (MI) defined as AMI in men &lt; 55 or women &lt; 65 still maintains high incidence compared to the known decrease in AMI in the elderly over the year. Hypothesis: Our study sought to assess the trend of premature MI using a nationally representative sample Methods: This was a trend study of the National Inpatient database (NIS) from 2010 to 2019. We searched for premature MI as the reason for hospitalization using the ICD codes for AMI in females and males less than 65 and 55 respectively. We estimated trends, inpatient mortality, mean length of hospital stay (LOS) and mean total hospital charges (THC) over the studied period. We performed a stratified analysis in categories: sex (male and female), race (Hispanics, Blacks and Caucasians), and median household income for patient's zip code (low-income quartile [LIQ] : 1-$49,999 vs high-income quartile [HIQ]: &gt;$86,000) to assess disparities in outcomes. Multivariable regression analysis adjusted for age and sex was used to obtain trend statistics on outcomes Results: There was a total of 637,173 hospitalizations for premature MI with 58.6% of a them being females. The proportion of females rose by 4.2% in 2010 compared to 2019. Premature MI proportion increased by 43% in Hispanics, 16.4% in Blacks and 4.6% among Caucasians. LIQ had a 8.9% increase in Premature MI while the HIQ had a 10% reduction. There was no significant increase in incidence of premature MI over the time period. Average mortality in female was 2.1% compared to 1.5% in males. Average mortality rate for the time period under study was 1.82% with a 13.7% decrease in mortality over the studied decade. Mortality decreased by 15.2% and 13.6% among females and males respectively. Mortality among Caucasian was 1.72% and decreased by 233.8%, while mortality following premature MI was 1.9% in blacks and decreased by 22.6%. There was trend towards decreasing mean LOS with a 33.2% increase in THC. Conclusions: There appears to be an increased incidence of Premature MI amongst women and LIQ households. Also, among the three studied races, the Hispanic race had the highest rise in the incidence of premature MI.
Abstract 15306: Nocturnal Hypertension is Associated With Hypertension Mediated Organ Damage Independent of Twenty-Four Blood Pressure in Hypertension
Authors: Azra Mahmud, Ruba Allhadaib, Nawaf A Alhabdan, Mohammad H Alkhidri, Bernard Silke
Journal: Circulation (2022)

Introduction: The new 2017 American College of Cardiology/American Heart Association guidelines propose that blood pressure (BP) measured during the awake period (clinic BP and ambulatory BP) should be controlled to &lt;130/80 mm Hg as a universal BP goal. However, even after controlling daytime BPs, there is still a residual risk in hypertension, i.e., nocturnal hypertension. It has been well-established that night-time BP during sleep is closely associated with cardiovascular events in both community-dwelling subjects and hypertensive patients. Hypothesis: We hypothesized that nocturnal hypertension is associated is associated with hypertension-mediated organ damage (HMOD) in hypertensive patients. Methods: All subjects underwent the following procedures: 2-D and Doppler echocardiography, spot urine microalbuminuria (MA), arterial stiffness using pulse wave velocity (PWV) and ambulatory BP monitoring over 24-h periods. Nocturnal hypertension was defined according to current guidelines (i.e., nighttime systolic BP (SBP) ≥110 and/or diastolic BP ≥70 mm Hg). Results: Among 2375 subjects, (mean age 55±12 years, 45% female), nocturnal hypertension was evident in more than half of the study population with some 43% being masked uncontrolled nocturnal hypertension. Compared to the patients without nocturnal hypertension, the prevalence of left ventricular hypertrophy, increased relative wall thickness, MA and PWV&gt;12m/s in patients with nocturnal hypertension was significantly higher at 25%, 64%, 56%, and 55%, respectively. In multivariate logistic regression analyses, after adjusting for other risk factors, nocturnal BP was associated with HMOD, independent of daytime BP. Conclusions: Nocturnal hypertension is a strong independent risk factor for HMOD, highlighting the importance of early detection and control of this particular BP phenotype in hypertensive patients.
Abstract 15372: Machine Learning Distinguishes Continuous Risk of Gastrointestinal Bleeding, Stroke, and Death in Ambulatory Lvad Patients
Authors: Palak Shah, Gabriel T Sayer, Shashank S Sinha, Manreet Kanwar, Jennifer Cowger, Francis D Pagani, Aditi Nayak, Mandeep Mehra, Joseph C Cleveland, Mitchell Psotka, Ramesh Singh, Shashank Desai, Qianhui Lu, Yajing Hu, ALLISON T CONNOLLY, Robert Kormos, Nir Uriel
Journal: Circulation (2022)

Introduction: Advanced data analytics are needed to reliably predict bleeding and thrombotic risk in ambulatory left ventricular assist device (LVAD) patients. Hypothesis: Machine learning techniques can be used to predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory LVAD patients. Methods: HeartMate 3 TM LVAD recipients from the MOMENTUM 3 studies with up to 2-year follow-up were included. A multistate model was developed with 5-fold cross-validation to characterize the continuous probability of events after discharge. Model features included pre-implant, index implant, and short- and long-term post-implant clinical features. 85% of patients were used for model derivation and 15% for validation. Model performance was assessed with area under the curve (AUC). With the model features, a risk stratification tool was created by dividing patients’ into terciles of predicted risk. Results: Among 2,056 LVAD patients who survived to hospital discharge, the median age was 59.4 yrs (20.4% Female, 28.6% Black). At 2-years, the incidence of GIB, Stroke, and Death was 25.6%, 6.0% and 12.3%, respectively. Unique models including pre-implant, implant and post-implant features were created for GIB (Figure A), Stroke and Death. In ambulatory LVAD patients, the model could predict 30-day risk of GIB at any time post-implant which was 26.9%, 2.6% and 0.8% in high, medium and low-risk patients respectively (Figure B). Similar risk prediction was performed for stroke and death. The cross-validated AUC in the derivation cohort was 0.70, 0.69, and 0.85 for GIB, stroke, and death respectively. Conclusion: We developed an innovative risk tool informed by machine learning techniques that predicts risk of GIB, stroke, and death at any 30-day interval in ambulatory LVAD patients with readily available clinical data. The model allows for risk stratification that accurately predicts future events and may be useful to guide clinical decision making.
Abstract 15594: Decreasing the High Risk of Ponatinib-Induced Cardiovascular Toxicity in Chronic Myeloid Leukemia
Authors: Anna P Hnatiuk Hnatiuk, Arne A Bruyneel, Dhanir Taylor, Mallesh Pandrala, Arpit Dheeraj, Wenqi Li, Ricardo Serrano, Dries Feyen, Michelle Vu, Prashila Amatya, Gupta Saloni, Yusuke Nakauchi, Isabel Morgado, Volker Wiebking, Ronglih Liao, Matthew Porteus, Ravindra Majeti, Sanjay Malhotra, Mark Mercola
Journal: Circulation (2022)

Introduction: Cardiovascular (CV) toxicity of cancer therapeutics is a growing problem. Ponatinib is one of the most cardiotoxic Tyrosine Kinase Inhibitors (TKIs) and is used as a highly effective TKI against ABL T315I mutation in Chronic Myeloid Leukemia (CML). Long-term exposure to ponatinib increases CV events including myocardial infarction, heart failure, stroke, peripheral vascular disease and venous thrombosis. There is need of novel therapeutics to provide treatment for CML while avoiding CV toxicity. Hypothesis: Using in vitro and in vivo models of CV toxicity can make possible to reengineer ponatinib to minimize its toxicity. Methods: We developed new safer analogues of ponatinib using fragment-based approach. Their anti-tumor efficacy was tested in 2 different CML cell lines and CML patient samples. We assayed for myocardial toxicity by measuring contractile function in human iPSC-cardiomyocytes (hiPSC-CMs) using high-throughput functional imaging, for vascular toxicity by measuring vasculogenesis in human microvascular endothelial cells (HMVECs), and for bone marrow toxicity by colony formation assay in human bone marrow cells (HBMCs). Finally, we confirmed the safer CV profile and adequate anti-tumor efficacy in an in vivo xenograft mouse model of CML. Results: The new analogues inhibited T315I BCR-ABL kinase activity similar to ponatinib and suppressed T315I mutant CML tumor growth in vitro and in vivo . Compared to ponatinib, the new compounds showed markedly decreased adverse effects on contractility of hiPSC-CMs, vasculogenesis in HMVECs and bone marrow toxicity in HBMCs in vitro . The therapeutic window was increased in vivo , leading to regression of human T315I mutant CML xenografts comparable to ponatinib but without increased levels of cardiac troponin. Additionally, we identified multiple kinases, including FGFR1, that were inhibited by ponatinib but not the analogues, suggesting that there is a specific set of kinases responsible for ponatinib toxicity. Conclusions: This study demonstrates that chemical reengineering can generate novel, CV-safe TKIs that retain effective therapeutic properties against CML carrying ABL T315I mutation, but that exhibit minimal CV toxicity compared to ponatinib.